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At least 145 records · Page 8Linked to original sources

PubMed2003

Glutamate transporters in the guinea-pig cochlea: partial mRNA sequences, cellular expression and functional implications.

In the cochlea, glutamate plays a major role in synaptic transmission between the inner hair cell and the primary auditory neurons. Extracellular glutamate concentration must be regulated to prevent excitotoxicity. This regulation is mediated by excitatory amino acid transporters, membrane proteins that remove glutamate from the synaptic cleft. In this study, we investigated the distribution and activity of three excitatory amino acid transporters subtypes in the guinea-pig cochlea: glutamate aspartate transporter, glutamate transporter and excitatory amino acid carrier. A partial messenger ribonucleic acid sequence was determined for each of these transporters, by polymerase chain reaction with degenerate primers, using guinea-pig brain complementary deoxyribonucleic acid as the template. Primers specific for each transporter were then designed and used to screen a dissected organ of Corti complementary deoxyribonucleic acid library. The cellular distribution of each transporter was examined by immunocytochemistry. We investigated the functional consequences of inhibiting glutamate uptake by recording cochlear potentials during intracochlear perfusion with either l-trans-pyrrolidine-2,4-dicarboxylic acid or dihydrokainate. At the end of the electrophysiological session, cochleas were processed for electron microscopy. Only the glutamate aspartate transporter messenger ribonucleic acid was detected in the organ of Corti. Consistently, glutamate aspartate transporter protein was detected in the inner hair cell-supporting cells and in the ganglion of Corti satellite cells. Glutamate transporter and excitatory amino acid carrier were found in the afferent auditory neurons. Only intracochlear perfusions with l-trans-pyrrolidine-2,4-dicarboxylic acid resulted in a dose-dependent decrease in the amplitude of the cochlear compound action potential, leaving cochlear microphonic potential unaffected. After l-trans-pyrrolidine-2,4-dicarboxylic acid perfusion, cochleas displayed a swelling of the afferent endings typical of excitotoxicity. [(-)1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-4,5-dihydro-3-methylcarbamyl-2,3-benzodiazepine], a selective alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist protects the cochlea against l-trans-pyrrolidine-2,4-dicarboxylic acid effect.

Afferent Pathways↗

PubMed2001

Survival of neural stem cells in the cochlea.

Adult rat hippocampus-derived neural stem cells (NSCs) have been reported to have been successfully grafted in several brain regions. To evaluate the possibility of treatment of sensorineural hearing loss using NSCs, survival of NSCs in the cochlea was estimated. NSCs were grafted into newborn rat cochleas. Within 2-4 weeks of grafting to the cochlea, some NSCs survived in the cochlear cavity. Some of them had adopted the morphologies and positions of hair cells. This suggests that NSCs can adapt to the environment of the cochlea and gives hope for treatment of the damaged cochlea and sensorineural hearing loss.

Animals↗

PubMed2005

Expression of vascular endothelial growth factor and its receptors in the cochlea of various experimental animals.

CONCLUSION: The results of this study indicate that vascular endothelial growth factor (VEGF) may be an important regulator of the vascular network of the inner ear and suggest that the VEGF signalling pathway may play a role in pathophysiologic conditions. OBJECTIVE: In order to clarify the role of vascular growth factor in the modulation of the vascular network of the cochlea, we studied the expression of VEGF and its receptors-fms-like tyrosine kinase (Flt-1) and foetal liver kinase (Flk-1)-in the inner ear of 3-month-old rodents of different species: C57BL/6J mice, Wistar albino rats and Hartley albino guinea pigs. MATERIAL AND METHODS: Qualitative immunohistochemical studies were performed by using specific antibodies to VEGF and its receptors on paraffin sections of the cochlea. The expression levels of VEGF and its receptors were quantified by means of Western blot analysis of cochlea protein extracts. RESULTS: We demonstrated that VEGF and its receptors are expressed in the cochlea and described their distribution in the inner ear. In particular, VEGF and Flt-1 are present at the level of the modiolus, spiral ganglion, spiral ligament, basilar membrane, supporting cells, outer and inner hair cells and stria vascularis. Flk-1 was less strongly expressed in the cochlea and was not detected in the organ of Corti.

Animals↗

PubMed1999

Absence of mRNA encoding estrogen receptor in the rat cochlea.

Based on changes in hearing thresholds and tinnitus that are co-related with the menstrual cycle, it has been suggested that the cochlea may respond directly to estrogen. For this to occur, the cochlea should express estrogen receptors. In situ mRNA hybridization was performed on normal female rat cochleas, using radiolabeled RNA probes complementary to mRNA encoding estrogen receptor, to determine whether estrogen receptors are present in the cochlea. Strong hybridization of the riboprobes to sections of uterus and hypothalamus indicated that the technique detected estrogen receptor mRNA. No hybridization to any cochlear tissues was observed. The results indicate that estrogen receptors are not expressed on cochlear cells, at least in rats. This in turn suggests that variation in cochlear responses during the estrus cycle are not the result of the direct effect of estrogen on the cochlea. Such variation may, however, be caused by systemic changes in fluid regulation induced by estrogen receptors at a distant site, or by other hormone receptors.

Animals↗

PubMed1999

Hair cell loss in the aged guinea pig cochlea.

The various effects of ageing on the auditory system, collectively termed presbycusis, are being studied across a wide range of animal species, including humans. One contributing factor to presbycusis is thought to be losses of the sensory hair cells in the cochlea. In this study, hair cell counts were obtained from cochleas of pigmented guinea pigs (Cavia porcellus) at ages ranging from 11 days to 4 years 7 months, using scanning electron microscopy to visualize the organ of Corti. Representative samples of the basal, middle and apical turn of the cochlea were photographed for analysis. Hair cell loss was observed, even in young animals. However, the loss was greater in the aged animals, but was not distributed evenly throughout the length of the cochlea. No significant loss of hair cells was seen in the basal (high frequency) or middle turn of the cochlea of the aged animals. In the apical (low frequency) turn, there was a significant loss of hair cells in all rows of outer hair cells (up to around 20%), and was most severe in the third row. There was no loss of apical inner hair cells in the aged animals.

Aging↗

PubMed1999

Transgene expression in the guinea pig cochlea mediated by a lentivirus-derived gene transfer vector.

The utility of lentivirus as a gene delivery vector in the cochlea was evaluated in vitro and in vivo. Lentivirus transduction was assessed through expression analysis of a reporter gene, green fluorescent protein (GFP), integrated within the viral genome. In vitro characterization of lentivirus-GFP was assessed by infection of explants from cochleas of neonatal rat. The lentiviral vector transduced both spiral ganglion neurons (SGNs) and glial cells. In vivo characterization of lentivirus-GFP was assessed by directly infusing the vector into the guinea pig cochlea via an osmotic minipump. Sections of lentivirus-infused cochlea revealed a highly restricted fluorescence pattern limited to the periphery of the perilymphatic space. Transduction of SGNs and glial cells by lentivirus in vitro but not in vivo suggests limited dissemination of the viral vector from the perilymphatic space. The cellular and tissue architecture of the lentivirus-infused cochlea was intact and free of inflammation. Restricted transduction of cell types confined to the periphery of the perilymphatic space by the lentivirus is ideal for stable production of gene products secreted into the perilymph.

Animals↗

PubMed1999

Nitric oxide synthase in trigeminal ganglion cells projecting to the cochlea of rat and guinea pig.

Nitric oxide (NO) influences electrophysiological and morphological parameters of the mammalian cochlea. Recently, the isoform of the NO-producing enzyme neuronal NO synthase (nNOS) has been demonstrated in spiral ganglion cells and olivocochlear neurons. The cochlea is also innervated by fibers stemming from the trigeminal ganglion (TG) and superior cervical ganglion (SCG). Whether these ganglion cells contain nNOS is not known yet. We therefore identified TG and SCG cells upon injection of Fluoro-Gold (FG) into the cochlea and retrograde neuronal transport of FG in rat and guinea pig. These ganglion cells were investigated for neuronal NOS immunohistochemically. Perikarya labeled by FG were found in the ipsilateral TG and SCG. In both species investigated, a considerable number of FG-labeled TG cells were also nNOS-immunoreactive whereas SCG cells were not. These data, demonstrating the existence of nNOS-containing TG cells that project to the cochlea, provide evidence that these neurons are further sources of nitric oxide in the cochlea.

Animals↗

PubMed2002

ATP-gated ion channels assembled from P2X2 receptor subunits in the mouse cochlea.

Extracellular ATP has several neuro-humoral actions on cochlear physiology, many of which involve P2X receptor-mediated signal transduction. The present study extends the molecular physiology of P2X receptor gene expression in the cochlea to the principal platform for transgenic studies, the mouse model. P2X receptor subunits, which assemble to form ATP-gated ion channels, were localised in cryosections and whole-mount tissues from the adult mouse cochlea using a specific antiserum and immunoperoxidase histochemistry. Whole-cell voltage clamp recordings functionally correlated immunolocalisation of ATP-gated ion channels in isolated hair cells and supporting cells. P2X immunoreactivity was widespread throughout the epithelial lining of the cochlea (except vascular stria); spiral ganglion neurons, organ of Corti supporting cells, and outer hair cell (OHC) stereocilia exhibited strong P2X immunolabelling. Localisation of ATP-gated ion channels on the endolymphatic surface (cuticular plates and stereocilia) of outer hair cells was confirmed electrophysiologically. In contrast, Deiters' cells exhibited an even distribution of both immunolabelling over the whole cell membrane and inward currents could be evoked by localised ATP application anywhere on these cells. In both OHC and Deiters' cells, the slowly-desensitising inward currents were blocked by the P2X-selective antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), compatible with P2X subunits contributing to the ATP-gated ion channels. Our immunohistochemical and functional localisation of P2X receptors in the mouse cochlea extends previous studies to verify and characterise extracellular ATP signalling in the cochlea and extends support for P2X receptor-mediated regulation of endolymphatic ionic homeostasis, sound transduction, auditory neurotransmission and cochlear mechanics.

Adenosine Triphosphate↗

PubMed2001

Potassium recycling pathways in the human cochlea.

OBJECTIVES/HYPOTHESIS: Potential pathways for recycling potassium (K+) used in the maintenance of inner ear electrochemical gradients have been elucidated in animal models. However, little is known about K+ transport in the human cochlea. This study was designed to characterize putative K+ recycling pathways in the human ear and to determine whether observations from animal models can be extrapolated to humans. STUDY DESIGN: A prospective laboratory study using an immunohistochemical approach to analyze the distribution of key ion transport mediators in the human cochlea. METHODS: Human temporal bones were fixed in situ within 1 to 6 hours of death and subsequently harvested at autopsy. Decalcification was accomplished with the aid of microwaving. Immunohistochemical staining was then performed to define the presence and cell type-specific distribution of Na,K-ATPase, sodium-potassium-chloride cotransporter (NKCC), and carbonic anhydrase (CA) in the inner ear. RESULTS: Staining patterns visualized in the human cochlea closely paralleled those seen in other species. Anti-Na,K-ATPase stained strongly the basolateral plasma membrane of strial marginal cells and nerve endings underlying hair cells. This antibody also localized Na,K-ATPase to type II, type IV, and type V fibrocytes in the spiral ligament and in limbal fibrocytes. NKCC was present in the basolateral membrane of strial marginal cells as well as in type II, type V, and limbal fibrocytes. Immunoreactive carbonic anhydrase was present in type I and type III fibrocytes and in epithelial cells lining Reissner's membrane and the spiral prominence. CONCLUSIONS: The distribution of several major ion transport proteins in the human cochlea is similar but not identical to that described in various rodent models. These results support the presence of a complex system for recycling and regulating K+ homeostasis in the human cochlea, similar to that described in other mammalian species.

Animals↗

PubMed2002

High-resolution magnetic resonance imaging of human cochlea.

OBJECTIVES: High-resolution MRI (MRI) of human inner ear structures provides several advantages over other imaging modalities. High-resolution visualization of inner ear ultrastructure in a noninvasive manner may provide important information about inner ear disease that is not obtainable in other ways. The study was performed to demonstrate the capabilities of MRI at high resolution on the human cochlea, vestibular structures, and facial nerve. Comparative analyses of MRI anatomy with that seen on histological dissection were made. The aim of the study was to define the anatomy of human cadaveric cochlea using a 9.4-Tesla magnetic resonance scanner, currently the most powerful magnetic resonance magnet available. STUDY DESIGN: Experimental pilot study of cadaveric human cochleae. METHODS: Serial scanning using a 9.4-Tesla magnetic resonance imager on normal preserved and fresh cadaveric inner ears was performed in different planes. RESULTS: The images revealed detailed anatomy of the modiolus, utricle, saccule, semicircular canals, and facial nerve. Specifically, identifiable structures within the cochlea included the osseous spiral lamina, Reissner's membrane, membranous spiral lamina, spiral ligament, and others. CONCLUSIONS: Data established through the acquisition of images from cadaver cochlea, facial nerve, and vestibular complex provide a foundation for developing steps for testing temporal bones and, eventually, patients with Meniere's disease and other inner ear disease. The present ongoing project will provide information on baseline images of the inner ear using high-resolution MRI.

Cochlea↗

PubMed2006

Innervation of the apical turn of the human cochlea: a light microscopic and transmission electron microscopic investigation.

HYPOTHESIS: A light and transmission electron microscopic investigation of the apical turn of a freshly fixed human cochlea. BACKGROUND: Our knowledge about the human cochlea rests to a large extent on animal species research. An opportunity to obtain tissue from normal-hearing persons occurs during surgery for life-threatening petroclival meningioma. This study presents detail on the morphology and innervation of the apical part of the human cochlea using light microscopic and transmission electron microscopic level sectioning. METHODS: The tissue was histologically processed after removal during petroclival meningioma surgery. The cochlea was serially sectioned perpendicularly to its long axis, and at regular distances semithin sections were reembedded and prepared for transmission electron microscopy. Nerve fibers/fascicles were traced from the area of the spiral ganglion to the level of the inner hair cells, and a cochleotopic "map" of the cochlear nerve supplying the apical portion was constructed. RESULTS: The apical turn was found to be innervated by 3,694 myelinated nerve fibers representing approximately 10% of the total number of fibers innervating the cochlea. The total number of unmyelinated nerve fibers was 513. The majority belonged to the efferent olivocochlear system and the intraganglionic spiral bundle or represented Type II afferent neurons innervating outer hair cells. CONCLUSION: The significance of the anatomic findings in relation to cochlear implantation is discussed.

Adult↗

PubMed2004

Two-tone suppression and combination tone generation as computations performed by the Hopf cochlea.

Recent evidence suggests that the compressive nonlinearity responsible for the extreme dynamic range of the mammalian cochlea is implemented in the form of Hopf amplifiers. Whereas Helmholtz's original concept of the cochlea was that of a frequency analyzer, Hopf amplifiers can be stimulated not only by one, but also by neighboring frequencies. To reduce the resulting computational overhead, the mammalian cochlea is aided by two-tone suppression. We show that the laws governing two-tone suppression and the generation of combination tones naturally emerge from the Hopf-cochlea concept. Thus the Hopf concept of the cochlea reproduces not only local properties like the correct frequency response, but additionally accounts for more complex hearing phenomena that may be related to auditory signal computation.

Animals↗

PubMed1997

Mechanical responses to two-tone distortion products in the apical and basal turns of the mammalian cochlea.

Mechanical responses to one- and two-tone acoustic stimuli were recorded from the cochlear partition in the apical turn of the chinchilla cochlea, the basal turn of the guinea pig cochlea, and the hook region of the guinea pig cochlea. The most sensitive or "best" frequencies (BFs) for the sites studied were approximately 500 Hz, 17 kHz, and 30 kHz, respectively. Responses to the cubic difference tone (CDT), 2F1 - F2 (where F1 and F2 are the frequencies of the primary stimuli), were characterized at each site. Responses to the quadratic difference tone (QDT), F2 - F1, were also characterized in the apical turn preparations (QDT responses were too small to measure in the basal cochlea). The observed responses to BF QDTs and CDTs and to BF CDTs at each site appeared similar in many ways; the relative magnitudes of the responses were highest at low-to-moderate sound pressure levels (SPLs), for example, and the absolute magnitudes grew nonmonotonically with increases in the level of either primary (L1 or L2) alone. The peak effective levels of the CDT and QDT responses were also similar, at around -20 dB re L1 and/or L2. In other respects, however, the responses to CDTs and QDTs and to BF CDTs at each site behaved quite differently. At low-to-moderate SPLs, for example, most CDT phase leads decreased with increases in either L1 or L2, whereas most QDT phase leads increased with increasing L1 and varied little with L2. Most CDT responses also varied monotonically with equal-level primaries (i.e., when L1 = L2), whereas most QDT responses varied nonmonotonically. Different responses also varied in different ways when F1 and F2 were varied. Apical turn QDT responses were observed over a very wide F1/F2 range (F1 = 1-12 kHz), but were usually largest for stimuli <2-4 kHz. Apical turn CDT levels decreased (at rates of approximately 40-80 dB/octave) only when the frequency ratio F2/F1 increased beyond approximately 1.4-1.5. In the basal turn and hook regions, the CDT levels depended nonmonotonically on F2/F1 with the eventual rates of decrease being approximately 200 dB/octave. Optimal frequency ratios for the CDT increased from (F2 < 1.1F1) to (F2 approximately 1.2F1) with increasing SPL in the basal turn, but were stable at around F2/F1 approximately 1.05 in the hook region. CDT phase leads tended to increase with increasing F2/F1 in all three regions of the cochlea, particularly at low-to-moderate SPLs. These findings are discussed in relation to previous studies of cochlear mechanics, physiology, and psychophysics.

Acoustic Stimulation↗

PubMedDate not supplied

Stress pathways in the rat cochlea and potential for protection from acquired deafness.

Noise overstimulation will induce or influence intracellular molecular pathways in the cochlea. One of these is the 'classical' stress response pathway involving heat shock proteins. Hsp70 is induced in the cochlea by a wide variety of stresses including noise, hyperthermia and ototoxic drugs. When a stress that induces Hsp70 is applied to the cochlea, there is protection from a subsequent noise that would normally cause a permanent hearing loss. An upstream regulator of heat shock protein transcription, heat shock factor 1, is expressed in the cochlea and activated by stress. Mice lacking this heat shock factor have reduced recovery from noise-induced hearing loss. The same noise exposure that induces Hsp70 also increases the level of glial cell line-derived neurotrophic factor in the cochlea. Moreover, when this neurotrophic factor is applied into the perilymph of scala tympani prior to a noise exposure there is a significant reduction in hair cell loss and hearing loss. With the potential for activation of multiple pathways in the response to noise, gene microarrays can be useful to examine global gene expression. Initial studies examined differential gene expression immediately following a mild noise exposure (from which there is complete recovery) versus an intense noise (giving profound permanent deafness). Differential expression of several immediate early genes was found following the intense but not the mild noise exposure.

Animals↗

PubMed2006

Mechanical preprocessing of amplitude-modulated sounds in the apex of the cochlea.

Sound-evoked vibrations of individual Hensen's cells in the apical turn of a living guinea pig cochlea were recorded using a displacement-sensitive laser interferometer. The mechanical responses to amplitude-modulated (AM) tones were investigated, and are shown to be physiologically vulnerable. In the healthy cochlea, the AM responses are demodulated strongly at both moderate and high sound pressure levels. In the less healthy and postmortem cochlea, AM demodulation is weaker and is only seen at high stimulus levels. The physiologically vulnerable component of the demodulation is considered to be an analogue of the baseline position shifts that can be seen in the apical cochlea's responses to pure-tone stimuli, and is likely to originate in the cellular motility of the cochlea's outer hair cells.

Acoustic Stimulation↗

PubMed1994

Identification and localization of the GM1 ganglioside in the cochlea using thin-layer chromatography and cholera toxin.

Using high-performance thin-layer chromatography, we identified GM1, GM3, GD3, GD1a, GT1b, GQ1b, and other gangliosides in chinchilla cochlea and cerebellum. GM1 was also identified on chromatograms with the B-subunit of cholera toxin (BCT). BCT was also used to determine the distribution of GM1 in fixed and unfixed tissues from cochlea, cerebellum, and sciatic nerve. Positive control tissues showed expected labeling of GM1 by BCT. Negative controls showed expected suppression of BCT binding to GM1 after GM1 extraction and GM1 absorption. In the cochlea, GM1 appeared abundant in plasma membranes of most epithelial cells lining the endolymphatic surface of the scala media, including the interdental, inner supporting, pillar, Deiters, Hensen, Claudius, Boettcher, spiral prominence, and external sulcus. GM1 appeared less abundant in cells of the stria vascularis, Reissner's membrane, and in nerve fibers. In hair cells, the stereocilia appeared to contain GM1; however, the endolymphatic surface of the cuticular plate and the body of the outer hair cells appeared to contain little GM1. In addition, the tectorial membrane, connective tissue of the spiral limbus, and amorphous layer of the basilar membrane also appeared to contain little GM1. Enzymatic degradation of glycoproteins and transformation of polysialogangliosides to GM1 increased the reactivity of BCT to cochlear GM1. This further supported the presence of GM1 and other gangliosides in the cochlea. Although the functional significance of GM1 and other gangliosides in the cochlea is not yet known, they are likely to play important roles in membrane function.

Animals↗

PubMed1983

Morphological changes in the normal and neomycin-perfused guinea pig cochlea following chronic prosthetic implantation.

The effects of chronic prosthetic implantation and interval electrical stimulation were studied in the normal and neomycin-perfused cochlea of the guinea pig. One group of guinea pigs was implanted with a multiple-electrode prosthesis in the scala tympani. During a 4-week period, the device was stimulated for 3 hours weekly with a continuous, 1 kHz sinusoidal current of constant intensity. A second group of guinea pigs underwent identical implantation and stimulation except that cochlear perfusion with .1 M neomycin was performed at the time of implantation. Current intensities ranged from .1 to .6 mA RMS. Two complementary control groups were implanted but not stimulated. The animals were sacrificed, the cochleae were perfused with a fixative, and the temporal bones were prepared for examination under a light, transmission, or scanning electron microscope. In the electrically stimulated cochleae, degenerative changes occurred in both the inner and outer hair cells and supporting elements. A decrease was apparent in spiral ganglion cell and nerve fiber populations in areas of inner hair cell depletion and did not seem to correspond to the survival of supporting cells. The electrically active electrodes were uniformly surrounded by a connective tissue matrix and areas of immature bone. These changes occurred at all the intensities tested, and did not monotonically relate in severity to current intensity. None of the changes was apparent in the normal control ears. Morphological changes induced by the ototoxic drug neomycin were so severe is both stimulated and unstimulated cochleae that comparison was not possible; this form of pretreatment is apparently unsuitable for use in studies of electrically induced damage. It appears that in the normal animal, chronic implantation with interval electrical stimulation results in a cumulative form of sensory and neural damage histologically similar to that proceeding from chronic noise exposure as well as other ototoxic agents. Such effects should be minimized if surviving sensorineural and supporting elements in the functionally compromised cochlea are to be preserved.

Animals↗

PubMed1998

Age-related changes in the cochlea and cochlear nuclei of dogs.

To study the underlying morphological changes of presbycusis, cochlea and cochlear nuclei from twenty three dogs, ranging in age from 3 days to 17 years, were examined histologically. Dogs used in this study were house dogs kept in an environment similar to that of humans. Four types of histological changes reported in human presbycusis, that is, loss of spiral ganglion cells, atrophy of the organ of Corti, atrophy of the stria vascularis, and thickening of the basilar membrane were observed in dogs. The changes were prominent at the base of the cochlea. Less intense changes were also observed in the apex of the cochlea. The degree of these changes appeared to progress as a function of age. All four types of changes with varied intensity were found in all dogs over 12 years old. In addition to the changes in the cochlea, cochlear nuclei changes including nerve cell loss, astrogliosis and ubiquitin deposition were found in dogs over 10 years old. Hearing dysfunction was accompanied by the morphological changes, though the degree of the hearing dysfunction did not always parallel to that of morphological changes. The morphological changes seen in the cochlea and cochlear nuclei of dogs were qualitatively and quantitatively similar to those reported in aged humans, indicating that otopathologic changes in the inner ear may be due to aging plus exposure to certain environmental ototoxic factors.

Aging↗